Family with sequence similarity 83 member H (FAM83H)

Family with sequence similarity 83 member H (FAM83H) is a nuclear protein in humans encoded by the FAM83H gene, which is located on chromosome 8q24.3[1][3][6]. FAM83H is best known for its essential role in **tooth enamel formation**; mutations cause autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), a condition characterized by impaired mineralization of dental enamel[2][3][5]. The protein comprises 1179 amino acids and is rich in proline[1][6]. It contains two key domains: a phospholipase D-like (PLD-like) domain at the N-terminus (which is structurally similar to active PLDs but likely lacks enzymatic activity due to missing critical histidine), and a microtubule-binding domain at the C-terminus[1]. FAM83H is expressed throughout the body at low levels and not limited to dental tissues; it is found in liver, kidney, eyes, bladder, and larynx[1][3][7]. The protein is highly phosphorylated, can undergo sumoylation, is localized primarily to the nucleus, and interacts notably with casein kinase 1 isoforms (CK1) and keratins, suggesting roles in cytoskeletal organization and vesicle trafficking[1][5]. FAM83H also interacts with SEC16A, implicating it in ER-to-Golgi transport[5]. Beyond its developmental role, FAM83H is implicated in cancer biology: its expression is upregulated in several cancers (e.g., breast, liver, colorectal, prostate, ovary, pancreas, stomach)[2]. Increased or aberrant expression correlates with tumor progression, proliferation, poor prognosis (e.g., hepatocellular, uterine carcinoma), and may be a biomarker for disease aggression or prognosis[2]. Mechanistically, FAM83H may promote cancer cell proliferation, regulate keratin cytoskeleton, affect epithelial-mesenchymal transition (EMT), and is regulated by the oncogene MYC[2]. There are no known drugs targeting FAM83H, and no established mechanisms of action or safety concerns relating to targeting this molecule have been reported. The function of FAM83H outside of enamel formation and cancer biology remains incompletely understood[5].

Other names

FAM83HAI3AI3AFLJ46072Protein FAM83Hfamily with sequence similarity 83 member H